Preferential inhibition by ethanol of phorbol ester-induced smooth muscle contraction of guinea pig gallbladder.
In order to investigate how ethanol inhibits the contractility of gallbladder smooth muscle, the effects of different ethanol concentrations were examined on gallbladder contractile responses to stimulants which act on the smooth muscle by different mechanisms. A low concentration (25 mM) of ethanol significantly inhibited the contractile response to phorbol-12,13-dibutyrate (PDBu), but not that to KCl. It also did not significantly affect contractile response to Ca2+ ionophore A23187 in the presence of verapamil or that to Ba2+ in a medium without Ca2+. On the other hand, a higher concentration (200 mM) of ethanol significantly inhibited the contractile responses to PDBu, KCl, Ca2+ ionophore A23187 and BaCl2. These results together with our recent finding that PDBu-induced contraction of guinea pig gallbladder is completely dependent on activation of the voltage-dependent Ca2+ channel suggest that low concentrations of ethanol selectively inhibit the signal transduction of gallbladder smooth muscle cells in the pathway from activation of protein kinase C to that of the voltage-dependent Ca2+ channel, while high concentrations of ethanol inhibit the intracellular common pathway (probably in the cytoskeletal apparatus).
Masui
H
H
Department of Hygiene, Hyogo College of Medicine, Nishinomiya, Japan.
Wakabayashi
I
I
D000818:Animals; D017609:Barium Compounds / Q000494:pharmacology; D000001:Calcimycin / Q000494:pharmacology; D002118:Calcium / Q000494:pharmacology; D002492:Central Nervous System Depressants / Q000494:pharmacology*; D002712:Chlorides / Q000494:pharmacology; D004347:Drug Interactions; D004789:Enzyme Activation / Q000187:drug effects; D000431:Ethanol / Q000494:pharmacology*; D005704:Gallbladder / Q000187:drug effects* / Q000502:physiology; D006168:Guinea Pigs; D066298:In Vitro Techniques; D007476:Ionophores / Q000494:pharmacology; D008297:Male; D009119:Muscle Contraction / Q000187:drug effects*; D009130:Muscle, Smooth / Q000187:drug effects* / Q000502:physiology; D015240:Phorbol 12,13-Dibutyrate / Q000494:pharmacology*; D011189:Potassium Chloride / Q000494:pharmacology; D011493:Protein Kinase C / Q000378:metabolism; D012996:Solutions; D013268:Stimulation, Chemical
D017609:Barium Compounds; D002492:Central Nervous System Depressants; D002712:Chlorides; D007476:Ionophores; D012996:Solutions; C024986:barium chloride; D015240:Phorbol 12,13-Dibutyrate; D000001:Calcimycin; D000431:Ethanol; D011189:Potassium Chloride; D011493:Protein Kinase C; D002118:Calcium